PubMed Health⌕ Search

Biomedical subjects

T To

Publications and source records attributed to T To.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cerebroside sulfate activator protein (Saposin B): chromatographic and electrospray mass spectrometric properties.

Cerebroside sulfate activator protein is a small, heat-stable protein that is exceptionally resistant to proteolytic attack. This protein is essential for the catabolism of cerebroside sulfate and several other glycosphingolipids. Protein purified from pig kidney and human urine was extensively characterized by reversed-phase liquid chromatography and electrospray mass spectrometry. These two sources revealed 20 and 18 different molecular isoforms of the protein, respectively. Plausible explanations of the structures of the majority of these isoforms can be made on the basis of accurate molecular mass assignments. The reversed-phase chromatographic and electrospray mass spectrometric properties of enzymatically deglycosylated and disulfide-reduced protein were also compared. In addition to a demonstration of the power of electrospray ionization mass spectrometry for revealing a wealth of information on protein microheterogeneity and structural detail, the results also demonstrate the utility of this technique for monitoring spontaneous chemical and enzymatically mediated changes that occur as a result of metabolic processing and protein purification.

Animals↗
PubMed1999

Preparation of the cerebroside sulfate activator (CSAct or saposin B) from human urine.

The purification of cerebroside sulfate activator (CSAct) or saposin B from pooled human urine is described. Urinary proteins are concentrated by ammonium sulfate precipitation. A suspension of the precipitate is heat-treated and the heat-stable proteins are fractionated through a series of chromatographic steps. An initial concanavalin A column retains little of the CSAct activity, but is important for subsequent purification. Passing the Con A effluent directly onto an octyl Sepharose column removes the protein of interest which is recovered by affinity elution with octyl glucoside. Subsequent ion-exchange and gel filtration chromatographies yield a protein of 80-90% purity, although it is sometimes necessary to repeat one or more steps. A small amount of CSAct can sometimes be recovered from the initial Con A Sepharose column by methyl mannoside elution and purified by a parallel chromatographic protocol. Mass spectral analysis suggests that the final material is a mixture of two major and several minor glycoforms of a 79 amino acid protein with the structure predicted from the human prosaposin cDNA by truncation of both N- and C-terminal regions. Sugar analysis revealed the presence of glucosamine, mannose, and fucose, consistent with the major isoforms bearing a five-sugar Man(2)GluNac(2)Fuc or a single GluNac substituent. The human urinary material is similar to the previously characterized pig kidney protein in most respects, but varies in some details.

Amino Acids↗
PubMed1999

Effects of maternal antibodies on protection and development of antibody responses to human rotavirus in gnotobiotic pigs.

Although maternal antibodies can protect against infectious disease in infancy, they can also suppress active immune responses. The effects of circulating maternal antibodies, with and without colostrum and milk antibodies, on passive protection and active immunity to human rotavirus (HRV) were examined in gnotobiotic pigs. Pigs received intraperitoneal injections of high-titer serum (immune pigs [groups 1 and 2]) from immunized sows, low-titer serum from naturally infected sows (control pigs [groups 3 and 4]), or no serum (group 5). Immune or control colostrum and milk were added to the diet of groups 2 and 4, respectively. After inoculation (3 to 5 days of age) and challenge (postinoculation day [PID] 21) with virulent HRV, the effects of maternal antibodies on protection (from diarrhea and virus shedding), and on active antibody responses (measured by quantitation of antibody-secreting cells [ASC] in intestinal and systemic lymphoid tissues by ELISPOT) were evaluated. Groups 1 and 2 had significantly less diarrhea and virus shedding after inoculation but higher rates of diarrhea and virus shedding after challenge than did groups 3 and 5. Group 1 and 2 pigs had significantly fewer immunoglobulin A (IgA) ASC in intestinal tissues at PID 21 and at postchallenge day (PCD) 7 compared to group 5. Significantly fewer IgG ASC were present in the intestines of group 2 pigs at PID 21 and PCD 7 compared to group 5. There was a trend towards fewer ASC in intestinal tissues of group 2 than group 1, from PID 21 on, with significantly fewer IgA ASC at PCD 7. IgG ASC in the duodenum and mesenteric lymph nodes of group 3 and 4 pigs were significantly fewer than in group 5 at PCD 7. These decreases in ASC emphasize the role of passive antibodies in impairing induction of ASC rather than in merely suppressing the function of differentiated B cells. To be successful, vaccines intended for populations with high titers of maternal antibodies (infants in developing countries) may require higher titers of virus, multiple doses, or improved delivery systems, such as the use of microencapsulation or immune stimulating complexes, to overcome the suppressive effects of maternal antibodies.

Animals↗
PubMed1999

Oncogene expression and microvessel count in recurrent and nonrecurrent stage Ib squamous cell carcinoma of the cervix.

OBJECTIVE: To evaluate p53, epidermal growth factor receptor (EGFR) and c-erbB-2 oncogene expression and compare it with microvessel count (MVC) in determining the clinical outcome of stage Ib squamous cell carcinoma (SCC) of the cervix. STUDY DESIGN: Immunostaining with p53, EGFR, C-erbB-2 and factor VIII antibodies was performed on tumor sections from 22 patients (11 with cancer recurrence, 11 free of cancer after four years). The levels of oncogene expression were semiquantitatively graded (0-4). Microvessels were counted (per 200 x field) in areas of highest neovascularization. RESULTS: Eight of 11 patients (72.7%) with recurrence expressed EGFR as compared with 5 of 11 patients (45.5%) free of disease. This difference is not significant (P = .39). An equal number of patients with and without recurrence expressed c-erbB-2. Five of 11 patients (45.5%) with recurrence expressed p53, as compared with 6 of 11 (54.5%) free of disease (P = 1.00). Eight of 11 patients (72.7%) with recurrence had an MVC above 24 as compared with 2 of 11 patients (18.2%) free of disease; this difference was statistically significant (P = .03). CONCLUSION: The expression of EGFR, p53 and c-erbB-2 appears to have little prognostic value in stage Ib SCC of the uterine cervix. The prognostic value of MVC is in keeping with previous findings.

Adult↗
PubMed1999

Markov chain models and estimation of absolute progression rates: application to cataract progression in diabetic adults.

BACKGROUND: We present a case study in the use of Markov chain models of disease progression, with exponential regression to model the effects of covariates. METHODS: An exponential regression model was developed for a three-state Markov chain to model progression of cataracts in diabetic patients, with a view to estimation of absolute progression rates. Two methods of estimation were applied, a non-linear least squares approximation, and Markov Chain Monte Carlo (MCMC). RESULTS: Both methods gave estimated transition rates which can readily be transformed to absolute progression probabilities. Agreement was reasonable for most but not all of the parameters. CONCLUSIONS: The MCMC estimates had more conservative variance estimates.

Aged↗
PubMed1998

Cohort study on circumcision of newborn boys and subsequent risk of urinary-tract infection.

BACKGROUND: A decrease in risk of urinary-tract infection is one of the most commonly given reasons for circumcision of newborn boys. Previous studies have reported rates of UTI to be 10-20 times higher in uncircumcised than in circumcised boys. This population-based cohort study followed neonates in Ontario, Canada, prospectively to study the relation between circumcision and subsequent UTI risk. METHODS: Eligible boys were born to residents of Ontario between April 1, 1993, and March 31, 1994. We used hospital discharge data to follow up boys until March 31, 1996. FINDINGS: Of 69,100 eligible boys, 30,105 (43.6%) were circumcised and 38,995 (56.4%) uncircumcised. 888 boys circumcised after the first month of life were excluded. 29,217 uncircumcised boys were matched to the remaining circumcised boys by date of birth. The 1-year probabilities of hospital admission for UTI were 1.88 per 1000 person-years of observation (83 cases up to end of follow-up) in the circumcised cohort and 7.02 per 1000 person-years (247 cases up to end of follow-up) in the uncircumcised cohort (p<0.0001). The estimated relative risk of admission for UTI by first-year follow-up indicated a significantly higher risk for uncircumcised boys than for circumcised boys (3.7 [2.8-4.9]). 195 circumcisions would be needed to prevent one hospital admission for UTI in the first year of life. INTERPRETATION: Although our findings support the notion that circumcision may protect boys from UTI, the magnitude of this effect may be less than previously estimated.

Circumcision, Male↗
PubMed1998

Use of selective serotonin-reuptake inhibitors or tricyclic antidepressants and risk of hip fractures in elderly people.

BACKGROUND: Tricyclic antidepressants (TCAs) are associated with an increased risk of falls and hip fractures in elderly people. Selective serotonin-reuptake inhibitors (SSRIs) are reported to be better tolerated than TCAs. We investigated the risk of hip fractures associated with SSRIs and TCAs. METHODS: This case-control study used administrative healthcare data from the province of Ontario, Canada. 8239 cases-patients aged 66 years or older, treated in hospital between April, 1994, and March, 1995, for hip fracture-were each matched for age and sex to five controls. Logistic regression was used to calculate the odds ratio for hip fracture with adjustment for potential confounding effects produced by concomitant drug use and comorbidity. FINDINGS: With participants who had no exposure to antidepressants as the reference category, the adjusted odds ratio for hip fracture was 2.4 (95% CI 2.0-2.7) for exposure to SSRIs, 2.2 (1.8-2.8) for exposure to secondary-amine TCAs, and 1.5 (1.3-1.7) for exposure to tertiary-amine TCAs. For all types of antidepressants, current use was associated with a higher risk of hip fracture than former use. The odds ratios for hip fracture were higher for new current users than for continuous current users in all three drug classes. The proportion of current use in the low-dose range was 22% for SSRIs, 50% for secondary-amine TCAs, and 58% for tertiary-amine TCAs. INTERPRETATION: Exposure to any of the three classes of antidepressants is associated with a significant increase in the risk of hip fracture. Despite differences in dose distribution, this analysis suggests that SSRIs do not offer an advantage over TCAs in terms of risk of hip fracture.

Accidental Falls↗
PubMed1998

Quantitative immunolocalization of mu opioid receptors: regulation by naltrexone.

The present study utilized a newly developed quantitative immunohistochemical assay to measure changes in mu opioid receptor abundance following chronic administration of the opioid receptor antagonist naltrexone. These data were compared with those obtained from mu receptor radioligand binding on adjacent tissue sections, in order to determine whether the characteristic antagonist-induced increase in radioligand binding is due to an increase in the total number of mu receptors and/or to an increase in the proportion of receptors that are in an active binding conformation in the absence of a change in the total number of receptors. Adult male Sprague-Dawley rats were administered naltrexone, 7-8 mg/kg per day, or saline continuously for seven days by osmotic minipumps, after which time their brains were processed for immunohistochemistry and receptor autoradiography on adjacent fresh frozen tissue sections. Semiquantitative immunohistochemistry was performed using a radiolabelled secondary antibody for autoradiographic determination and a set of radioactive standards. Results demonstrate an overall concordance between the distribution of mu opioid receptors as measured by the two different methods with a few exceptions. Following naltrexone administration, mu receptor immunoreactivity was significantly higher in the amygdala, thalamus, hippocampus, and interpeduncular nucleus as compared with the saline-treated control animals. [3H]D-Ala2,N-Me-Phe4,Gly-ol5-enkephalin binding to mu opioid receptors was significantly higher in the globus pallidus, amygdala, thalamus, hypothalamus, hippocampus, substantia nigra, ventral tegmental area, central gray, and interpeduncular nucleus of the naltrexone-treated rats. These findings indicate that in some brain regions chronic naltrexone exposure increases the total number of mu opioid receptors, while in other regions there is an increase in the percent of active receptors without an observable change in the total number of receptors. Quantitative receptor immunodetection together with ligand autoradiography provides a new approach for investigating the regulation of mu opioid receptors on tissue sections.

Analgesics, Opioid↗
PubMed1997

Comparative studies of the pathogenesis, antibody immune responses, and homologous protection to porcine and human rotaviruses in gnotobiotic piglets.

Gnotobiotic piglets serve as a useful animal model for studies of rotavirus pathogenesis and immunity. An advantage over laboratory animal models is the prolonged susceptibility of piglets to rotavirus-induced disease, permitting an analysis of cross-protection and active immunity. Studies from our laboratory of the pathogenesis of human rotavirus infections in gnotobiotic piglets have confirmed that villous atrophy is induced in piglets given virulent but not attenuated human rotavirus (Wa strain) and have revealed that factors other than villous atrophy may contribute to the early diarrhea induced. To facilitate and improve rotavirus vaccination strategies, it is important to identify correlates of protective immunity. Comparison of antibody immune responses induced by infection with virulent porcine and human rotaviruses (mimic host response to natural infection) with those induced by live attenuated human rotavirus (mimic attenuated oral vaccines) in the context of homotypic protection has permitted an analysis of correlates of protective immunity. Our results indicate that the magnitude of the immune response is greatest in lymphoid tissues adjacent to the site of viral replication (small intestine). Secondly there was a direct association between the degree of protection induced and the level of the intestinal immune response, with primary exposure to virulent rotaviruses inducing significantly higher numbers of IgA ASC and complete protection against challenge. These studies thus have established basic parameters related to immune protection in the piglet model of rotavirus-induced disease, verifying the usefulness of this model to apply new strategies for the design and improvement of rotavirus vaccines.

Animals↗
PubMed1997

Physicians' opinions about decision aids for patients considering systemic adjuvant therapy for axillary-node negative breast cancer.

PURPOSE: To examine variations in physicians' opinions about the appropriateness and content of decision aids for women with breast cancer and criteria for their evaluation. METHODS: Cross-sectional survey of all 144 Ontario oncologists by Dillman's mailed survey design. The response rate was 87%. RESULTS: The predominant current practice pattern was to spontaneously inform patients about the treatment recommendations, degree of certainty regarding the recommendations, treatment regime, benefits and side effects. Most respondents (94%) endorsed patient decision aids, particularly when there was high uncertainty about providing adjuvant treatment. Over three-quarters endorsed measuring the following outcomes of decision aids: patients' clarity of trade-offs involved (e.g. survival vs. side effects); comprehension of treatment alternatives, risks and benefits; accuracy of expectations; decision satisfaction; anxiety; commitment to the decision; length of time to complete the decision aid; and decision uncertainty. The least support was for the use of the decision itself as an outcome measure. CONCLUSIONS: There is considerable consensus regarding the indications for, content and criteria for evaluating decision aids which should be considered when developing aids relevant to the needs of clinicians and patients.

Adult↗
PubMed1997

The Canadian National Breast Screening Study: update on breast cancer mortality.

The Canadian National Breast Screening Study (CNBSS), conducted on women age 40-49, was designed to evaluate the efficacy of combined annual mammography and physical examination of the breasts in reducing breast cancer mortality in comparison to usual care (UC) controls. From January 1980 through March 1985, 25,214 women were individually randomized to the mammography/physical exam (MP) arm and 25,216 to the UC. The integrity of the randomization has been reviewed and confirmed to be unbiased. During an average, follow-up of 10.5 years from entry (range: 8.75-13 years), 82 women died from breast cancer in the MP arm and 72 in the UC, for a rate ratio of 1.14 (95% confidence interval: 0.83-1.56). All-cause mortality was almost identical comparing the two groups; the nonsignificant excess of breast cancer deaths in the MP arm was balanced by an excess of other cancer deaths in the UC arm.

Adult↗
PubMed1996

Leukemia following occupational exposure to 60-Hz electric and magnetic fields among Ontario electric utility workers.

In a nested case-control study of 1,484 cancer cases and 2,179 matched controls from a cohort of 31,543 Ontario Hydro male employees, the authors evaluated associations of cancer risk with electric field exposure and reevaluated the previously reported findings for magnetic fields. Pensioners were followed from January 1, 1970, and active workers (including those who left the corporation) from January 1, 1973, with both groups followed through December 31, 1988. Exposures to electric and magnetic fields and to potential occupational confounders were estimated through job exposure matrices. Odds ratios were elevated for hematopoietic malignancies with cumulative electric field exposure. After adjustment, the odds ratio for leukemia in the upper tertile was 4.45 (95% confidence interval (CI) 1.01-19.7). Odds ratios were also elevated for acute nonlymphoid leukemia, acute myeloid leukemia, and chronic lymphoid leukemia. For cumulative magnetic field exposure, there were similar elevations that fell with adjustment. Evaluation of the combined effect of electric and magnetic fields for leukemia showed significant elevations of risk for high exposure to both, with a dose-response relation for increasing exposure to electric fields and an inconsistent effect for magnetic fields. There was some evidence of a nonsignificant association for brain cancer and benign brain tumors with magnetic fields. For lung cancer, the odds ratio for high exposure to electric and magnetic fields was 1.84 (95% CI 0.69-4.94).

Adult↗
PubMed1996

Immunohistochemical localization of ORL-1 in the central nervous system of the rat.

A novel member of the opioid receptor family (ORL-1) has been cloned from a variety of vertebrates. ORL-1 does not bind any of the classical opioids, although a high affinity endogenous agonist with close homology to dynorphin has recently been identified. We have generated a monoclonal antibody to the N-terminus of ORL-1 to map areas of receptor expression in rat central nervous system (CNS). Intense and specific immunolabeling was observed in multiple areas in the diencephalon, mesencephalon, pons/medulla, and spinal cord. In the telencephalon, intense labeling was observed in the neuropil throughout layers II-V in the neocortex, the anterior olfactory nuclear complex, the pyriform cortex, the CA1-CA4 fields and dentate gyrus of the hippocampus, and in many of the septal and basal forebrain areas. In contrast to other members of the opioid receptor family, light labeling for ORL-1 was observed in telencephalic areas such as caudate-putamen. In the cerebellum, ORL-1 immunoreactivity was only observed in the deep nuclei. Throughout the CNS the majority of labelling was localized to fiber processes and fine puncta, although labeled scattered perikarya were observed in a few brain areas such as the hilus dentate in the hippocampus and some nuclei in the brainstem and spinal cord. The present mapping study is consistent with the reported distribution of ORL-1 mRNA and provides the first immunohistochemical report on anatomical and cellular distribution of ORL-1 receptor in the rat CNS.

Animals↗
PubMed1996

Tumor angiogenesis as a predictor of recurrence in stage Ib squamous cell carcinoma of the cervix.

OBJECTIVE: To explore the possibility of using histologic microvessel count of sections from the tumor to predict recurrence of stage Ib squamous cell carcinoma of the cervix. METHODS: Tumor sections from 22 patients (11 patients free of disease after 3 years and 11 patients with recurrence) were stained histoimmunochemically for factor VIII-related antigens. Vessel counting in the most active area of angiogenesis was performed by two pathologists on a x 200 microscopic field (0.739 mm2) without knowledge of the patient's' outcome. To predict recurrence, vessel count was compared with age, tumor size, tumor grade, lymph-vascular invasion, duration of follow-up, and type of therapy. RESULTS: Only high microvessel count (mean 19.9, range 7-43, versus mean 30.1, range 17-78; P < .05) and tumor size (mean 2.84 cm, range 1-4.2, versus mean 4.11 cm, range 2.2-6; P < .05) were independent factors predicting recurrence. CONCLUSION: High microvessel count in tumors may be used to predict recurrence in stage Ib squamous cell carcinoma of the cervix.

Adult↗
PubMed1996

Respiratory function after cardiac surgery.

STUDY OBJECTIVE: Cardiac surgery is complicated by decreased postoperative respiratory muscle strength and spirometry with accompanying increased atelectasis. The specific respiratory symptoms attributable to these physiologic changes are unknown, and this study looked at the symptoms and underlying physiology. DESIGN: Convenience sampling of observational cohort. SETTING: Tertiary care university hospital. PATIENTS: One hundred thirty-eight patients undergoing elective surgery were enrolled. INTERVENTIONS: Changes from admission to 8-week postoperative values in atelectasis, pleural effusions, spirometry (forced vital capacity and forced expiratory volume in one second), and respiratory muscle strength (negative inspiratory pressure) were measured. These physiologic changes were compared with changes in respiratory symptoms of cough, wheeze, phlegm, and dyspnea on walking up a slight hill noted from admission to 8-week follow-up by stepward logistic regression. MEASUREMENTS AND RESULTS: Spirometry and negative inspiratory pressure decreased and atelectasis increased from admission to discharge. These disturbances had only incompletely resolved at 8-week follow-up. Some patients reported fewer symptoms of cough (11%), phlegm (9%), wheeze (35%), and dyspnea (46%) at 8 weeks follow-up. Other patients reported increased symptoms of cough (15%), phlegm (10%), wheeze (6%), and dyspnea (4%) at 8 weeks follow-up. Residual atelectasis at 8 weeks was predictive of fewer symptoms of dyspnea (odds ratio [OR] 0.335, p = 0.199; 95% confidence interval [CI] 0.188, 0.597), increased symptoms of dyspnea (OR 855, p = 0.006; 95% CI 6.6, 11052), and increased symptoms of cough (OR 260, p = 0.023; 95% CI 2.13, 31829). Negative inspiratory pressure at 8 weeks was predictive of fewer symptoms of dyspnea (OR 1.05, p = 0.032; 95% CI 1.02, 1.09) and increased symptoms of wheeze (OR 0.7, p = 0.45; 95% CI 0.533, 0999). Forced vital capacity at 8 weeks was predictive of increased symptoms of wheeze (OR 0.005; p = 0.015; 95% CI 0.0060, 0.775). CONCLUSIONS: Postoperative changes in respiratory muscle strength and spirometry can persist up to at least 8 weeks postoperatively. Many patients report a change in respiratory symptoms of cough, phlegm, dyspnea, or wheeze. The change in respiratory symptoms at 8 weeks is correlated with residual respiratory muscle weakness, decrease in spirometry, and residual atelectasis.

Adult↗
PubMed1996

Trends and variations in the use of vascular surgery in Ontario.

OBJECTIVE: To measure changes over time in overall surgical rates and geographic rate variations for three major vascular procedures (abdominal aortic aneurysm repairs, peripheral vascular disease procedures and carotid endarterectomies). BACKGROUND: There is little research literature on population-based usage profiles of vascular procedures. The three procedures profiled were all subject to marked shifts in evidence or surgical opinions, raising the issue of the interplay between temporal trends and geographic variations in their use. METHODS: Based on Ontario's hospital discharge abstracts and census data, population-based usage rates were calculated by site of patient residence from 1981 to 1991. Extent of rate variation was summarized with the coefficient of variation, systematic component of variation and the adjusted-likelihood ratio chi2. Spearman rank correlations were also calculated to assess stability of county rankings for each procedure. RESULTS: The overall rates of peripheral vascular procedures and repair for abdominal aortic aneurysms fell 24% and increased 42% respectively. The overall rate of carotid endarterectomies dropped from 46/100,000 in 1981 to 20/100,000 in 1989, but by 1991 had increased to 37/100,000. Through the decade measures of variation fell minimally for all three procedures. CONCLUSION: Overall use of vascular procedures shifted in apparent response to new research evidence and technologies. Despite marked changes in surgical rates, the extent of geographic variation was stable, suggesting that differing factors influence overall surgical rates and geographic rate variations. Audit at the local level using primary clinical data is needed to understand why disparities in use persist.

Aortic Aneurysm, Abdominal↗
PubMed1996

A cohort study on childhood asthma admissions and readmissions.

BACKGROUND: Admissions to hospitals for childhood asthma seem to be increasing, even though admissions for other childhood conditions are decreasing. We studied admissions and readmissions for childhood asthma in Ontario in an attempt to uncover factors relating to the admission patterns. METHODS: Using the hospital discharge data from the Canadian Institute for Health Information, 28,646 children with diagnoses of asthma were identified from April 1, 1989, to March 31, 1992. RESULTS: The admission rates for asthma among children in Ontario showed a 14.8% decrease from 1987 to 1992. This decline was observed primarily in 5- to 17-year-olds. Younger children had a fourfold risk of hospital admission for asthma. In the 4 years studied, 10,427 children (36.4%) were readmitted at least once, representing 22,114 readmissions, 16,196 (73.2%) of which were for asthma. The 6-month probabilities of readmission for asthma were 20.0% (0- to 4-year-olds) and 11.7% (5- to 17-year-olds). The estimated relative risks (RRs) indicated that younger children had a significantly higher risk of readmission for asthma (RR, 1.38; 95% confidence interval, 1.30 to 1.46) or asthma-related causes (RR, 5.02; 95% confidence interval, 4.16 to 6.05). CONCLUSIONS: The observed increasing trend in admissions for asthma among children in the 1970s and 1980s leveled off in the early 1990s. The declining admission rates were largely caused by the lower admission rates among school-aged children from 5 to 17 years. The relatively high admission and readmission rates of preschool children are still a concern. Further research is necessary to examine factors that influence admissions for asthma among young children.

Adolescent↗